#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

B Cells Enhance Antigen-Specific CD4 T Cell Priming and Prevent Bacteria Dissemination following Genital Tract Infection


B cells can contribute to acquired immunity against intracellular bacteria, but do not usually participate in primary clearance. Here, we examined the endogenous CD4 T cell response to genital infection with Chlamydia muridarum using MHC class-II tetramers. Chlamydia-specific CD4 T cells expanded rapidly and persisted as a stable memory pool for several months after infection. While most lymph node Chlamydia-specific CD4 T cells expressed T-bet, a small percentage co-expressed Foxp3, and RORγt-expressing T cells were enriched within the reproductive tract. Local Chlamydia-specific CD4 T cell priming was markedly reduced in mice lacking B cells, and bacteria were able to disseminate to the peritoneal cavity, initiating a cellular infiltrate and ascites. However, bacterial dissemination also coincided with elevated systemic Chlamydia-specific CD4 T cell responses and resolution of primary infection. Together, these data reveal heterogeneity in pathogen-specific CD4 T cell responses within the genital tract and an unexpected requirement for B cells in regulating local T cell activation and bacterial dissemination during genital infection.


Vyšlo v časopise: B Cells Enhance Antigen-Specific CD4 T Cell Priming and Prevent Bacteria Dissemination following Genital Tract Infection. PLoS Pathog 9(10): e32767. doi:10.1371/journal.ppat.1003707
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003707

Souhrn

B cells can contribute to acquired immunity against intracellular bacteria, but do not usually participate in primary clearance. Here, we examined the endogenous CD4 T cell response to genital infection with Chlamydia muridarum using MHC class-II tetramers. Chlamydia-specific CD4 T cells expanded rapidly and persisted as a stable memory pool for several months after infection. While most lymph node Chlamydia-specific CD4 T cells expressed T-bet, a small percentage co-expressed Foxp3, and RORγt-expressing T cells were enriched within the reproductive tract. Local Chlamydia-specific CD4 T cell priming was markedly reduced in mice lacking B cells, and bacteria were able to disseminate to the peritoneal cavity, initiating a cellular infiltrate and ascites. However, bacterial dissemination also coincided with elevated systemic Chlamydia-specific CD4 T cell responses and resolution of primary infection. Together, these data reveal heterogeneity in pathogen-specific CD4 T cell responses within the genital tract and an unexpected requirement for B cells in regulating local T cell activation and bacterial dissemination during genital infection.


Zdroje

1. StarnbachMN, RoanNR (2008) Conquering sexually transmitted diseases. Nature reviews Immunology 8: 313–317.

2. US Department of Health and Human Services (2012) Sexually Transmitted Disease Surveillance 2011. Available: http://www.cdc.gov/std/stats11/Surv2011.pdf

3. GottliebSL, BermanSM, LowN (2010) Screening and treatment to prevent sequelae in women with Chlamydia trachomatis genital infection: how much do we know? The Journal of infectious diseases 201 Suppl 2: S156–167.

4. GottliebSL, MartinDH, XuF, ByrneGI, BrunhamRC (2010) Summary: The natural history and immunobiology of Chlamydia trachomatis genital infection and implications for Chlamydia control. The Journal of infectious diseases 201 Suppl 2: S190–204.

5. HaggertyCL, GottliebSL, TaylorBD, LowN, XuF, et al. (2010) Risk of sequelae after Chlamydia trachomatis genital infection in women. The Journal of infectious diseases 201 Suppl 2: S134–155.

6. GottliebSL, BrunhamRC, ByrneGI, MartinDH, XuF, et al. (2010) Introduction: The natural history and immunobiology of Chlamydia trachomatis genital infection and implications for chlamydia control. The Journal of infectious diseases 201 Suppl 2: S85–87.

7. BrunhamRC, Rey-LadinoJ (2005) Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine. Nature reviews Immunology 5: 149–161.

8. CotterTW, RamseyKH, MiranpuriGS, PoulsenCE, ByrneGI (1997) Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice. Infection and immunity 65: 2145–2152.

9. PerryLL, SuH, FeilzerK, MesserR, HughesS, et al. (1999) Differential sensitivity of distinct Chlamydia trachomatis isolates to IFN-gamma-mediated inhibition. Journal of immunology 162: 3541–3548.

10. PerryLL, FeilzerK, CaldwellHD (1997) Immunity to Chlamydia trachomatis is mediated by T helper 1 cells through IFN-gamma-dependent and -independent pathways. Journal of immunology 158: 3344–3352.

11. CainTK, RankRG (1995) Local Th1-like responses are induced by intravaginal infection of mice with the mouse pneumonitis biovar of Chlamydia trachomatis. Infection and immunity 63: 1784–1789.

12. MorrisonRP (2000) Differential sensitivities of Chlamydia trachomatis strains to inhibitory effects of gamma interferon. Infection and immunity 68: 6038–6040.

13. CohenCR, KoochesfahaniKM, MeierAS, ShenC, KarunakaranK, et al. (2005) Immunoepidemiologic profile of Chlamydia trachomatis infection: importance of heat-shock protein 60 and interferon- gamma. J Infect Dis 192: 591–599.

14. CotterTW, MengQ, ShenZL, ZhangYX, SuH, et al. (1995) Protective efficacy of major outer membrane protein-specific immunoglobulin A (IgA) and IgG monoclonal antibodies in a murine model of Chlamydia trachomatis genital tract infection. Infection and immunity 63: 4704–4714.

15. MorrisonSG, SuH, CaldwellHD, MorrisonRP (2000) Immunity to murine Chlamydia trachomatis genital tract reinfection involves B cells and CD4(+) T cells but not CD8(+) T cells. Infection and immunity 68: 6979–6987.

16. MorrisonSG, MorrisonRP (2005) A predominant role for antibody in acquired immunity to chlamydial genital tract reinfection. Journal of immunology 175: 7536–7542.

17. SuH, FeilzerK, CaldwellHD, MorrisonRP (1997) Chlamydia trachomatis genital tract infection of antibody-deficient gene knockout mice. Infection and immunity 65: 1993–1999.

18. RamseyKH, SoderbergLS, RankRG (1988) Resolution of chlamydial genital infection in B-cell-deficient mice and immunity to reinfection. Infection and immunity 56: 1320–1325.

19. YangX, BrunhamRC (1998) Gene knockout B cell-deficient mice demonstrate that B cells play an important role in the initiation of T cell responses to Chlamydia trachomatis (mouse pneumonitis) lung infection. Journal of immunology 161: 1439–1446.

20. BrunhamRC, KuoC, ChenWJ (1985) Systemic Chlamydia trachomatis infection in mice: a comparison of lymphogranuloma venereum and trachoma biovars. Infection and immunity 48: 78–82.

21. KarunakaranKP, Rey-LadinoJ, StoynovN, BergK, ShenC, et al. (2008) Immunoproteomic discovery of novel T cell antigens from the obligate intracellular pathogen Chlamydia. Journal of immunology 180: 2459–2465.

22. MoonJJ, ChuHH, HatayeJ, PaganAJ, PepperM, et al. (2009) Tracking epitope-specific T cells. Nature protocols 4: 565–581.

23. LeeSJ, McLachlanJB, KurtzJR, FanD, WinterSE, et al. (2012) Temporal expression of bacterial proteins instructs host CD4 T cell expansion and Th17 development. PLoS pathogens 8: e1002499.

24. YuH, JiangX, ShenC, KarunakaranKP, JiangJ, et al. (2010) Chlamydia muridarum T-cell antigens formulated with the adjuvant DDA/TDB induce immunity against infection that correlates with a high frequency of gamma interferon (IFN-gamma)/tumor necrosis factor alpha and IFN-gamma/interleukin-17 double-positive CD4+ T cells. Infection and immunity 78: 2272–2282.

25. RoanNR, GierahnTM, HigginsDE, StarnbachMN (2006) Monitoring the T cell response to genital tract infection. Proceedings of the National Academy of Sciences of the United States of America 103: 12069–12074.

26. McSorleySJ, AschS, CostalongaM, ReinhardtRL, JenkinsMK (2002) Tracking salmonella-specific CD4 T cells in vivo reveals a local mucosal response to a disseminated infection. Immunity 16: 365–377.

27. BoldTD, BanaeiN, WolfAJ, ErnstJD (2011) Suboptimal activation of antigen-specific CD4+ effector cells enables persistence of M. tuberculosis in vivo. PLoS pathogens 7: e1002063.

28. BeattyWL, ByrneGI, MorrisonRP (1993) Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proceedings of the National Academy of Sciences of the United States of America 90: 3998–4002.

29. JohnsonRM, YuH, KerrMS, SlavenJE, KarunakaranKP, et al. (2012) PmpG303-311, a protective vaccine epitope that elicits persistent cellular immune responses in Chlamydia muridarum-immune mice. Infection and immunity 80: 2204–2211.

30. KochMA, Tucker-HeardG, PerdueNR, KillebrewJR, UrdahlKB, et al. (2009) The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nature immunology 10: 595–602.

31. WoolardMD, HensleyLL, KawulaTH, FrelingerJA (2008) Respiratory Francisella tularensis live vaccine strain infection induces Th17 cells and prostaglandin E2, which inhibits generation of gamma interferon-positive T cells. Infect Immun 76: 2651–2659.

32. PepperM, LinehanJL, PaganAJ, ZellT, DileepanT, et al. (2010) Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells. Nature immunology 11: 83–89.

33. ZhangZ, ClarkeTB, WeiserJN (2009) Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 119: 1899–1909.

34. MorrisonSG, MorrisonRP (2000) In situ analysis of the evolution of the primary immune response in murine Chlamydia trachomatis genital tract infection. Infection and immunity 68: 2870–2879.

35. MosemanEA, IannaconeM, BosurgiL, TontiE, ChevrierN, et al. (2012) B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity. Immunity 36: 415–426.

36. PerryLL, HughesS (1999) Chlamydial colonization of multiple mucosae following infection by any mucosal route. Infection and immunity 67: 3686–3689.

37. Votte-LambertA, JolyJP, BecuweC, EbF, CapronJP, et al. (1990) Chlamydia trachomatis peritonitis: another cause of protein-rich lymphocytic ascites. Journal of clinical gastroenterology 12: 341–343.

38. WallaceTM, HartWR (1991) Acute chlamydial salpingitis with ascites and adnexal mass simulating a malignant neoplasm. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 10: 394–401.

39. GuagentiRC, BermanAL, CohenNN (1989) Chlamydial ascites. Digestive diseases and sciences 34: 139–141.

40. PunnonenR, TerhoP, KlemiPJ (1982) Chlamydial pelvic inflammatory disease with ascites. Fertility and sterility 37: 270–272.

41. ScidmoreMA (2005) Cultivation and Laboratory Maintenance of Chlamydia trachomatis. Current protocols in microbiology Chapter 11: Unit 11A 11.

42. YuH, JiangX, ShenC, KarunakaranKP, BrunhamRC (2009) Novel Chlamydia muridarum T cell antigens induce protective immunity against lung and genital tract infection in murine models. Journal of immunology 182: 1602–1608.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2013 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#